A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice.
A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice.
复制标题
单次注射腺病毒疫苗可提供血凝素茎介导的保护，以对抗小鼠异亚型流感攻击。
DOI：
10.1016/j.ymthe.2022.01.011
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发表时间：
2022-05-04
影响因子：
12.4
通讯作者：
Coughlan, Lynda
中科院分区：
文献类型：
--
作者：
Bliss, Carly M.;Freyn, Alec W.;Caniels, Tom G.;Leyva-Grado, Victor H.;Nachbagauer, Raffael;Sun, Weina;Tan, Gene S.;Gillespie, Virginia L.;McMahon, Meagan;Krammer, Florian;Hill, Adrian V. S.;Palese, Peter;Coughlan, Lynda
关键词：
传统的流感疫苗不能提供广泛的保护，以防止具有大流行潜力的多种甲型流感病毒。开发通用流感病毒疫苗的努力包括将免疫重新集中到流感病毒表面糖蛋白，血凝素（HA）的高度保守的茎结构域。我们构建了一个非复制腺病毒（Ad）载体，编码H1 HA的分泌形式，以评估HA茎聚焦免疫。在小鼠中测试了Ad5_H1疫苗在单次免疫方案中对同源、异源和异亚型致命攻击产生广泛的交叉反应保护的能力。Ad5_H1引发血凝抑制（HI+）活性抗体（Abs），对同源H1N1攻击具有100%的杀菌保护作用。此外，除了刺激CD4+和CD8+茎特异性T细胞应答外，Ad5_H1还能快速诱导具有fc介导效应功能活性的h1茎特异性抗体。这种免疫表型提供了100%的保护，免受头部不匹配的致命攻击，重组流感病毒以茎介导的方式携带嵌合HA cH6/1。最重要的是，在单次接种Ad5_H1疫苗后，观察到对异亚型禽流感病毒H5N1致命攻击后的死亡率有100%的保护。总之，基于ad的流感疫苗可以在幼稚动物中产生广泛的保护作用，可以考虑用于大流行的准备和储存。Bliss和他的同事在他们的手稿中表明，用腺病毒载体疫苗编码一种分泌形式的透明质酸进行单次免疫，可以引起广泛的交叉反应性透明质酸茎特异性细胞和体液免疫反应，从而在同源、异源和异亚型致命攻击中提供保护。
Conventional influenza vaccines fail to confer broad protection against diverse influenza A viruses with pandemic potential. Efforts to develop a universal influenza virus vaccine include refocusing immunity towards the highly conserved stalk domain of the influenza virus surface glycoprotein, hemagglutinin (HA). We constructed a non-replicating adenoviral (Ad) vector, encoding a secreted form of H1 HA, to evaluate HA stalk-focused immunity. The Ad5_H1 vaccine was tested in mice for its ability to elicit broad, cross-reactive protection against homologous, heterologous, and heterosubtypic lethal challenge in a single-shot immunization regimen. Ad5_H1 elicited hemagglutination inhibition (HI+) active antibodies (Abs), which conferred 100% sterilizing protection from homologous H1N1 challenge. Furthermore, Ad5_H1 rapidly induced H1-stalk-specific Abs with Fc-mediated effector function activity, in addition to stimulating both CD4+ and CD8+ stalk-specific T cell responses. This phenotype of immunity provided 100% protection from lethal challenge with a head-mismatched, reassortant influenza virus bearing a chimeric HA, cH6/1, in a stalk-mediated manner. Most importantly, 100% protection from mortality following lethal challenge with a heterosubtypic avian influenza virus, H5N1, was observed following a single immunization with Ad5_H1. In conclusion, Ad-based influenza vaccines can elicit significant breadth of protection in naive animals and could be considered for pandemic preparedness and stockpiling. In their manuscript, Bliss and colleagues show that a single-shot immunization with an adenoviral vectored vaccine encoding a secreted form of HA can elicit broadly cross-reactive HA-stalk-specific cellular and humoral immune responses, which confer protection in homologous, heterologous, and heterosubtypic lethal challenge.
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影响因子：
17.1
作者：
Andrews SF;Huang Y;Kaur K;Popova LI;Ho IY;Pauli NT;Henry Dunand CJ;Taylor WM;Lim S;Huang M;Qu X;Lee JH;Salgado-Ferrer M;Krammer F;Palese P;Wrammert J;Ahmed R;Wilson PC
通讯作者：
Wilson PC
影响因子：
5.4
作者：
Chen, H.;Xiang, Z. Q.;Ertl, H. C. J.
通讯作者：
Ertl, H. C. J.
影响因子：
5.5
作者：
Afkhami, Sam;LeClair, Daniel A.;Xing, Zhou
通讯作者：
Xing, Zhou
影响因子：
5.1
作者：
Croyle, MA;Cheng, X;Wilson, JM
通讯作者：
Wilson, JM
影响因子：
7.8
作者：
Clemens EB;van de Sandt C;Wong SS;Wakim LM;Valkenburg SA
通讯作者：
Valkenburg SA